Onset model of mutually catalytic self-replicative systems formed by an assembly of polynucleotides.

Self-replicability is a unique attribute observed in all living organisms, and the question of how the life was physically initiated could be equivalent to the question of how self-replicating informative polymers were formed in the abiotic material world. It has been suggested that the present DNA and proteins world was preceded by an RNA world in which genetic information of RNA molecules was replicated by the mutual catalytic function of RNA molecules. However, the important question of how the transition occurred from a material world to the very early pre-RNA world remains unsolved both experimentally and theoretically. We present an onset model of mutually catalytic self-replicative systems formed in an assembly of polynucleotides. A quantitative expression of the critical condition for the onset of growing fluctuation towards self-replication in this model is obtained by analytical and numerical calculations.

Transition from an antiphase error-correction mode to a synchronization mode in mutual hand tracking.

Proactive motion in hand tracking and in finger bending, in which the body motion occurs prior to the reference signal, has been previously reported when a periodic target signal was shown to the subjects at relatively high frequencies. These phenomena indicate that the human sensory-motor system tends to choose an anticipatory mode rather than a reactive mode, when the target motion is relatively fast. The present research was undertaken to study what kind of mode appears in the sensory-motor system when two persons were asked to track the hand position of the partner at various mean tracking frequency. The experimental results showed that a transition from a mutual error-correction mode to a synchronization mode occurred in the same region of the transition frequency with the one from a reactive error-correction mode to a proactive anticipatory mode reported previously in the target tracking experiments of the single subjects. Present research indicated that synchronization of body motion occurred only when both of the pair subjects operated in a proactive anticipatory mode. We also presented mathematical models to explain the behavior of the error-correction mode and the synchronization mode.

Migration of Dictyostelium slugs: anterior-like cells may provide the motive force for the prespore zone.

The collective motion of cells in a biological tissue originates from their individual responses to chemical and mechanical signals. The Dictyostelium slug moves as a collective of up to 100,000 cells with prestalk cells in the anterior 10-30% and prespore cells, intermingled with anterior-like cells (AL cells), in the posterior. We used traction force microscopy to measure the forces exerted by migrating slugs. Wild-type slugs exert frictional forces on their substratum in the direction of motion in their anterior, balanced by motive forces dispersed down their length. StlB- mutants lack the signal molecule DIF-1 and hence a subpopulation of AL cells. They produce little if any motive force in their rear and immediately break up. This argues that AL cells, but not prespore cells, are the motive cells in the posterior zone. Slugs also exert large outward radial forces, which we have analyzed during "looping" movement. Each time the anterior touches down after a loop, the outward forces rapidly develop, approximately normal to the almost stationary contact lines. We postulate that these forces result from the immediate binding of the sheath to the substratum and the subsequent application of outward "pressure," which might be developed in several different ways.

Semianalytical transient solution of a delayed differential equation and its application to the tracking motion in the sensory-motor system.

We derived semianalytically the transient solution of a delayed differential equation that had been shown to be a simple but good model of the sensory-motor system. In the present Brief Report, we applied this transient solution for studying the global nature of the transient tracking motion when visual target information is changed suddenly. The results clarified that the dynamic error minimization principle in hand motion observed experimentally is robust over a wide range of the parameter space of the delay time, the time constant, and the feedforward parameter.

An iterative method to calculate forces exerted by single cells and multicellular assemblies from the detection of deformations of flexible substrates.

We present a new method for quantification of traction forces exerted by migrating single cells and multicellular assemblies from deformations of flexible substrate. It is based on an iterative biconjugate gradient inversion method. We show how the iteration and the solution are influenced by experimental parameters such as the noise on deformations sigma ( XY ), and the mean depth of recorded deformations Z (M). In order to find the validity range of our computational method, we simulated two different patterns of force. The first artificial force pattern mimics the forces exerted by a migrating Dictyostelium slug at a spatial resolution of Delta=20 mum (Rieu et al. in Biophys J 89:3563-3576, 2005) and corresponds to a large and spread force field. The second simulated force pattern mimics forces exerted by a polarized fibroblast at discrete focal adhesion sites separated by Delta=4 microm. Our iterative method allows, without using explicit regularization, the detailed reconstruction of the two investigated patterns when noise is not too high (sigma ( XY )/u (max)< or =6%, where u (max )is the maximal deformation), and when the plane of recorded deformations is close to the surface (Delta/Z (M)> or =4). The method and the required range of parameters are particularly suitable to study forces over large fields such as those observed in multicellular assemblies.

Direct mechanical force measurements during the migration of Dictyostelium slugs using flexible substrata.

We use the flexible substrate method to study how and where mechanical forces are exerted during the migration of Dictyostelium slugs. This old and contentious issue has been left poorly understood so far. We are able to identify clearly separate friction forces in the tip and in the tail of the slug, traction forces mostly localized in the inner slug/surface contact area in the prespore region and large perpendicular forces directed in the outward direction at the outline of contact area. Surprisingly, the magnitude of friction and traction forces is decreasing with slug velocity indicating that these quantities are probably related to the dynamics of cell/substrate adhesion complexes. Contrary to what is always assumed in models and simulations, friction is not of fluid type (viscous drag) but rather close to solid friction. We suggest that the slime sheath confining laterally the cell mass of the slug experiences a tension that in turn is pulling out the elastic substrate in the direction tangential to the slug profile where sheath is anchored. In addition, we show in the appendix that the iterative method we developed is well adapted to study forces over large and continuous fields when the experimental error is sufficiently low and when the plane of recorded bead deformations is close enough to the elastomer surface, requirements fulfilled in this experimental study of Dictyostelium slugs.

Human hand moves proactively to the external stimulus: an evolutional strategy for minimizing transient error.

We investigated particularly the proactive nature of the visual-motor system by steady and transient experiments of a hand-tracking task, and confirmed that the hand motion precedes on the average the target motion in steady runs within a finite frequency range of the sinusoidal target motion. The question why and how much the hand motion should precede was answered by frequency-jump experiments. The results implied that the positive phase shift of the hand motion represents the proactive nature of the visual-motor control system which is adaptationally developed for each person to minimize the transient error of the hand motion when the target motion changes unexpectedly.

Cell movements and mechanical force distribution during the migration of dictyostelium slugs.

Migration of Dictyostelium discoideum slugs results from coordinated movement of their constituent cells. It is generally assumed that each cell contributes to the total motive force of the slug. However, the basic mechanisms by which mechanical forces (traction and resistive forces) are transmitted to the substrate, their magnitude and their location, are largely unknown. In this work, we performed detailed observations of cell movements by fluorescence microscopy using two-dimensional (2D) slugs. We show that 2D slugs share most of the properties of 3D ones. In particular, waves of movement propagate in long 2D slugs, and slug speed correlates with slug length as found in 3D slugs. We also present the first measurements of the distribution of forces exerted by 2D and 3D slugs using the elastic substrate method. Traction forces are mainly exerted in the central region of the slug. The large perpendicular forces around slug boundary and the existence of parallel resistive forces in the tip and/or the tail suggest an important role of the sheath in the transmission of forces to the substrate.

Rapid patterning and zonal differentiation in a two-dimensional Dictyostelium cell mass: the role of pH and ammonia.

Recently it was demonstrated that a rapidly forming, self-organizing pattern that emerges within two-dimensional Dictyostelium discoideum cell cultures could later give rise to stripes of distinct zones, each comprising different cell types. Here we report physiological aspects of the initial rapid patterning and its relationship to cell differentiation. We found that as the temperature is lowered the characteristic length of the pattern increases. From this we estimated the activation energy of the patterning kinetics. Fluorescence of fluorescein-conjugated dextran revealed that the cytosolic pH of cells in the inside zone becomes lower than that in the outer zone facing the air. The patterning could be inhibited by addition of the plasma-membrane proton pump inhibitors diethystilbestrol (DES) or miconazole. Preincubation of cells with weak acid delayed the timing of the patterning, whereas weak base hastened it. A pH-indicating dye revealed localized accumulation of ammonia in the extracellular space. These results suggest that gradients of secreted metabolites may be directly responsible for the rapid patterning and its consequence on cell differentiation in a confined geometrical situation. Possible diffusible candidate molecules and a reaction scheme coupled to the imposed oxygen gradient are discussed.